2,995 research outputs found

    Realistic litz wire characterization using fast numerical simulations

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    The losses of realistic litz wires are characterized while explicitly accounting for their construction, using a procedure that computes the current-driven and magnetic-field-driven copper losses using fast numerical simulations. We present a case study that examines loss variation in one- and two-level litz wires as a function of twisting pitch, over a wide range of values and in small increments. Experimental confirmation is presented for predictions made by numerical simulations. Results confirm the capability and efficiency of numerical methods to provide valuable insights into the realistic construction of litz wire.MIT Energy InitiativeSingapore-MIT Allianc

    Bunshi doryokugaku shimyureshon o mochiita mizubunshi to seitai busshitsu no sogo sayo no kaimei

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    The role of zinc (Zn2+), a modulator of N-methyl-D-aspartate (NMDA) receptors, in regulating long-term synaptic plasticity at hippocampal CA1 synapses is poorly understood. The effects of exogenous application of Zn2+ and of chelation of endogenous Zn2+ were examined on long-term potentiation (LTP) of stimulus-evoked synaptic transmission at Schaffer collateral (SCH) synapses in field CA1 of mouse hippocampal slices using whole-cell patch clamp and field recordings. Low micromolar concentrations of exogenous Zn2+ enhanced the induction of LTP, and this effect required activation of NMDA receptors containing NR2B subunits. Zn2+ elicited a selective increase in NMDA/NR2B fEPSPs, and removal of endogenous Zn2+ with high-affinity Zn2+ chelators robustly reduced the magnitude of stimulus-evoked LTP. Taken together, our data show that Zn2+ at physiological concentrations enhances activation of NMDA receptors containing NR2B subunits, and that this effect enhances the magnitude of LTP

    Altered Gene Expression in the Schistosome-Transmitting Snail Biomphalaria glabrata following Exposure to Niclosamide, the Active Ingredient in the Widely Used Molluscicide Bayluscide

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    In view of the call by the World Health Organization (WHO) for elimination of schistosomiasis as a public health problem by 2025, use of molluscicides in snail control to supplement chemotherapy–based control efforts is likely to increase in the coming years. The mechanisms of action of niclosamide, the active ingredient in the most widely used molluscicides, remain largely unknown. A better understanding of its toxicology at the molecular level will both improve our knowledge of snail biology and may offer valuable insights into the development of better chemical control methods for snails. We used a recently developed Biomphalaria glabrata oligonucleotide microarray (31K features) to investigate the effect of sublethal exposure to niclosamide on the transcriptional responses of the snail B. glabrata relative to untreated snails. Most of the genes highly upregulated following exposure of snails to niclosamide are involved in biotransformation of xenobiotics, including genes encoding cytochrome P450s (CYP), glutathione S-transferases (GST), and drug transporters, notably multi-drug resistance protein (efflux transporter) and solute linked carrier (influx transporter). Niclosamide also induced stress responses. Specifically, six heat shock protein (HSP) genes from three super-families (HSP20, HSP40 and HSP70) were upregulated. Genes encoding ADP-ribosylation factor (ARF), cAMP response element-binding protein (CREB) and coatomer, all of which are involved in vesicle trafficking in the Golgi of mammalian cells, were also upregulated. Lastly, a hemoglobin gene was downregulated, suggesting niclosamide may affect oxygen transport. Our results show that snails mount substantial responses to sublethal concentrations of niclosamide, at least some of which appear to be protective. The topic of how niclosamide’s lethality at higher concentrations is determined requires further study. Given that niclosamide has also been used as an anthelmintic drug for decades and has been found to have activity against several types of cancer, our findings may be of relevance in understanding how both parasites and neoplastic cells respond to this compound

    pH dependence of cyanide and imidazole binding to the heme domains of \u3cem\u3eSinorhizobium meliloti\u3c/em\u3e and \u3cem\u3eBradyrhizobium japonicum\u3c/em\u3e FixL

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    Equilibrium and kinetic properties of cyanide and imidazole binding to the heme domains of Sinorhizobium meliloti and Bradyrhizobium japonicum FixL (SmFixLH and BjFixLH) have been investigated between pH 5 and 11. KD determinations were made at integral pH values, with the strongest binding at pH 9 for both ligands. KD for the cyanide complexes of BjFixLH and SmFixLH is 0.15 ± 0.09 and 0.50 ± 0.20 μM, respectively, and 0.70 ± 0.01 mM for imido-BjFixLH. The association rate constants are pH dependent with maximum values of 443 ± 8 and 252 ± 61 M−1 s−1 for cyano complexes of BjFixLH and SmFixLH and (5.0 ± 0.3) × 104 and (7.0±1.4) × 104M−1 s−1 for the imidazole complexes. The dissociation rate constants are essentially independent of pH above pH 5; (1.2 ± 0.3) × 10−4 and (1.7 ± 0.3) × 10−4 s−1 for the cyano complexes of BjFixLH and SmFixLH, and (73±19) and (77±14) s−1 for the imidazole complexes. Two ionizable groups in FixLH affect the rate of ligand binding. The more acidic group, identified as the heme 6 propionic acid, has a pKa of 7.6 ± 0.2 in BjFixLH and 6.8 ± 0.2 in SmFixLH. The second ionization is due to formation of hydroxy-FixLH with pKa values of 9.64± 0.05 for BjFixLH and 9.61 ± 0.05 for SmFixLH. Imidazole binding is limited by the rate of heme pocket opening with maximum observed values of 680 and 1270 s−1 for BjFixLH and SmFixLH, respectively

    Factor VIII:C concentrate purified from plasma using monoclonal antibodies: human studies

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    Conventional clotting factor concentrates have, until recently, been of intermediate purity, containing less than 1% of the coagulation factor, and greater than 99% extraneous plasma proteins such as fibrinogen, fibronectin, gamma globulins, and traces of many others. We report here the results of a new factor VIII concentrate that is purified from human plasma using a mouse monoclonal antibody to factor VIII:vWF in an affinity chromatography system. The resultant concentrate has an activity of between 3,000 and 5,000 U/mg protein before albumin is added as a stabilizer. Seven patients with severe hemophilia A and no inhibitor who were positive for antibody to human immunodeficiency virus (HIV) have been treated solely with this concentrate for over 24 months. Factor usage in these patients has ranged from 611 U/kg/yr to 2,022 U/kg/yr. These patients have infused approximately once per week on the average, most often for joint hemorrhages. The efficacy of the concentrate is excellent. No allergic reactions have occurred and no factor VIII antibodies have developed. In these seven patients mean CD4 counts stabilized (856 +/- 619 at screen v 778 +/- 686 at 24 months) and there was reversal of skin test anergy. In a comparison group on conventional intermediate purity concentrate chosen retrospectively decreases in mean CD4 cell counts similarly did not occur. However, the number of the comparison patients who were anergic increased over the course of the study. These observations indicate the possibility that more highly purified concentrates may stabilize immune function in HIV seropositive patients

    Dietary patterns of early childhood and maternal socioeconomic status in a unique prospective sample from a randomized controlled trial of Prenatal DHA Supplementation

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    A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Background Dietary habits established in early childhood and maternal socioeconomic status (SES) are important, complex, interrelated factors that influence a child’s growth and development. The aim of this study was to define the major dietary patterns in a cohort of young US children, construct a maternal SES index, and evaluate their associations. Methods The diets of 190 children from a randomized, controlled trial of prenatal supplementation of docosahexaenoic acid (DHA) were recorded at 6-mo intervals from 2-4.5 years by 24-h dietary recall. Hierarchical cluster analysis of age-adjusted, average daily intake of 24 food and beverage groups was used to categorize diet. Unrotated factor analysis generated an SES score from maternal race, ethnicity, age, education, and neighborhood income. Results We identified two major dietary patterns: “Prudent” and “Western.” The 85 (45%) children with a Prudent diet consumed more whole grains, fruit, yogurt and low-fat milk, green and non-starchy vegetables, and nuts and seeds. Conversely, those with a Western diet had greater intake of red meat, discretionary fat and condiments, sweet beverages, refined grains, French fries and potato chips, eggs, starchy vegetables, processed meats, chicken and seafood, and whole-fat milk. Compared to a Western diet, a Prudent diet was associated with one standard deviation higher maternal SES (95% CI: 0.80 to 1.30). Conclusions We found two major dietary patterns of young US children and defined a single, continuous axis of maternal SES that differed strongly between groups. This is an important first step to investigate how child diet, SES, and prenatal DHA supplementation interact to influence health outcomes. Trial registration NCT00266825. Prospectively registered on December 15, 2005 Electronic supplementary material The online version of this article (doi:10.1186/s12887-016-0729-0) contains supplementary material, which is available to authorized users

    Lidar Validation Measurements at the NOAA Mauna Loa Observatory NDACC Station

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    NASA's Goddard Space Flight Center (GSFC) transported two lidar instruments to the NOAA facility at the Mauna Loa Observatory (MLO) on the Big Island of Hawaii, to participate in an official, extended validation campaign. This site is situated 11,141 ft. above sea level on the side of the mountain. The observatory has been making atmospheric measurements regularly since the 1950's, and has hosted the GSFC Stratospheric Ozone (STROZ) Lidar and the GSFC Aerosol and Temperature (AT) Lidar on several occasions, most recently between November, 2012 and November, 2015. The purpose of this extended deployment was to participate in Network for the Detection of Atmospheric Composition Change (NDACC) Validation campaigns with the JPL Stratospheric Ozone Lidar and the NOAA Temperature, Aerosol and Water Vapor instruments as part of the routine NDACC Validation Protocol

    Pharmacological Inhibition and Activation of the Ca2+ Activated Cl− Channel TMEM16A

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    TMEM16A is a Ca2+ activated Cl- channel with important functions in airways, intestine, and other epithelial organs. Activation of TMEM16A is proposed as a therapy in cystic fibrosis (CF) to reinstall airway Cl- secretion and to enhance airway surface liquid (ASL). This CFTR-agnostic approach is thought to improve mucociliary clearance and lung function in CF. This could indeed improve ASL, however, mucus release and airway contraction may also be induced by activators of TMEM16A, particularly in inflamed airways of patients with asthma, COPD, or CF. Currently, both activators and inhibitors of TMEM16A are developed and examined in different types of tissues. Here we compare activation and inhibition of endogenous and overexpressed TMEM16A and analyze potential off-target effects. The three well-known blockers benzbromarone, niclosamide, and Ani9 inhibited both TMEM16A and ATP-induced Ca2+ increase by variable degrees, depending on the cell type. Niclosamide, while blocking Ca2+ activated TMEM16A, also induced a subtle but significant Ca2+ store release and inhibited store-operated Ca2+ influx. Niclosamide, benzbromarone and Ani9 also affected TMEM16F whole cell currents, indicating limited specificity for these inhibitors. The compounds Eact, cinnamaldehyde, and melittin, as well as the phosphatidylinositol diC8-PIP2 are the reported activators of TMEM16A. However, the compounds were unable to activate endogenous TMEM16A in HT29 colonic epithelial cells. In contrast, TMEM16A overexpressed in HEK293 cells was potently stimulated by these activators. We speculate that overexpressed TMEM16A might have a better accessibility to intracellular Ca2+, which causes spontaneous activity even at basal intracellular Ca2+ concentrations. Small molecules may therefore potentiate pre-stimulated TMEM16A currents, but may otherwise fail to activate silent endogenous TMEM16A

    Advanced Configurations for Very Large Subsonic Transport Airplanes

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    Recent aerospace industry interest in developing a subsonic commercial transport airplane with 50 percent greater passenger capacity than the largest existing aircraft in this category (the Boeing 747-400 with approximately 400-450 seats) has generated a range of proposals based largely on the configuration paradigm established nearly 50 years ago with the Boeing B-47 bomber. While this basic configuration paradigm has come to dominate subsonic commercial airplane development since the advent of the Boeing 707/Douglas DC-8 in the mid-1950's, its extrapolation to the size required to carry more than 600-700 passengers raises several questions. To explore these and a number of related issues, a team of Boeing, university, and NASA engineers was formed under the auspices of the NASA Advanced Concepts Program. The results of a Research Analysis focused on a large, unconventional transport airplane configuration for which Boeing has applied for a patent are the subject of this report. It should be noted here that this study has been conducted independently of the Boeing New Large Airplane (NLA) program, and with the exception of some generic analysis tools which may be common to this effort and the NLA (as will be described later), no explicit Boeing NLA data other than that published in the open literature has been used in the conduct of the study reported here
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